Azathioprine

Azathioprine is a prescription medication used to treat rheumatoid arthritis. It is also used in kidney transplant patients to prevent rejection of the new kidney. Azathioprine belongs to a group of drugs called immunosuppressive antimetabolites, which work by decreasing the activity of the body's immune system so it will not attack the transplanted organ or the joints.

This medication comes in tablet form and is taken once or twice a day, with or without food.

This medication is also available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Common side effects of azathioprine include nausea, vomiting, hair loss, and rash.

Azathioprine gets broken down in the body by proteins called enzymes. Azathioprine gets converted in the body to a product (known as a metabolite) that can be toxic at high levels. An enzyme known as TMPT breaks down this metabolite so that you do not experience its harmful effects. Some patients have a change (called a mutation) in this enzyme that prevents it from breaking down the toxic metabolite properly.

Some patients have a mutation in TMPT that prevents it from breaking down toxic metabolites. These patients are more likely to experience toxic effects including the potential for lowered blood counts. A test can determine whether your TMPT enzymes carry such a mutation. Your doctor may change your dose of azathioprine based on your test results. Your doctor should also monitor your blood counts while you are being treated with azathioprine.

Oral/Injectable:

Azathioprine is a prescription medication used in the following conditions:

• to prevent transplant rejection, or to prevent an attack of the transplanted organ by the immune system
• to treat severe rheumatoid arthritis, a condition in which the body attacks its own joints, causing pain, swelling, and loss of function

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Azathioprine may be found in some form under the following brand names:

• Azasan

• Imuran

Oral/Injectable:

Serious side effects have been reported with azathioprine. See the “Azathioprine Precautions” section.

Common side effects of azathioprine include the following:

• nausea
• vomiting
• hair loss
• rash
• diarrhea
• fever
• muscle aches
• hair loss

This is not a complete list of azathioprine side effects. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• allopurinol (Zyloprim, Aloprim, Lopurin)
• aminosalicylates such as mesalamine (Apriso, Asacol, Pentasa), olsalazine (Dipentum), and sulfasalazine (Azulfidine)
• blood thinners such as warfarin (Coumadin, Jantoven)
• trimethoprim/sulfamethoxazole (Bactrim, Septra)
• ribavirin (Copegus, Rebetol, Ribasphere, Virazole)
• alkylating medications such as cyclophosphamide (Cytoxan), chlorambucil (Amboclorin), and melphalan (Alkeran)
• angiotensin-converting enzyme (ACE) inhibitors such as:
  • benazepril (Lotensin, Lotensin HCT)
  • captopril (Capoten, Capozide)
  • enalapril (Vasotec, Vaseretic)
  • fosinopril (Monopril, Monopril HCT)
  • lisinopril (Prinivil, Prinzide, Zestril, Zestoretic)
  • moexipril (Univasc, Uniretic)
  • quinapril (Accupril, Accuretic, Quinaretic)
  • ramipril (Altace)
  • trandolapril (Mavik, Tarka)

This is not a complete list of azathioprine drug interactions. Ask your doctor or pharmacist for more information.

Oral/Injectable:

Serious side effects have been reported with azathioprine including the following:

• lowered blood counts. This is medically known as bone marrow suppression. Your doctor will want to monitor for this, as bone marrow suppression can lead to thrombocytopenia, anemia, and leukopenia.
  • thromobocytopenia. This is a condition in which your blood has a lower than normal number of blood cell fragments called platelets. Tell your healthcare provider right away if you have the following signs and symptoms of thrombocytopenia:
    • mild to serious bleeding
    • purple, brown, and red bruises (purpura)
    • small red or purple dots on your skin (petechiae)
    • prolonged bleeding, even from minor cuts
    • bleeding or oozing from the mouth or nose, especially nosebleeds or bleeding from brushing your teeth
    • abnormal vaginal bleeding (especially heavy menstrual flow)
    • blood in the urine or stool or bleeding from the rectum. Blood in the stool can appear as red blood or as a dark, tarry color. Taking iron supplements also can cause dark, tarry stools.
    • headaches and other neurological symptoms. These problems are very rare, but you should discuss them with your doctor.
  • anemia. This is a condition in which your blood has a lower than normal number of red blood cells. Tell your healthcare provider right away if you have the following signs and symptoms of anemia:
    • shortness of breath
    • dizziness
    • headache
    • coldness in the hands and feet
    • pale skin
    • chest pain
  • leukopenia. This is a condition when there are a low number of white blood cells in your body. These cells help fight infections. You may become more susceptible to infections and even to negative reactions of live vaccines if you are taking azathioprine. Tell your healthcare provider if you are feeling “under the weather” or are running a fever. Also, let your healthcare provider know if you are scheduled to receive a vaccination, as live vaccinations can make you sick.
• decline in liver function. Tell your healthcare provider if you have any signs or symptoms of liver damage, which include the following:
  • yellowing of the skin or eyes
  • nausea
  • vomiting
  • fatigue
  • itching
• gastrointestinal (stomach and bowel) hypersensitivity reaction. Tell your healthcare provider right away if you have any or all of the following symptoms of a gastrointestinal hypersensitivity reaction:
  •  severe nausea
  • severe vomiting
  • diarrhea
  • rash
  • fever
  • muscle aches
  • occasionally hypotension (low blood pressure)

Do not take azathioprine if you:

• are allergic to azathioprine or to any of its ingredients
• have rheumatoid arthritis and are also pregnant
• are also taking alkylating medications such as cyclophosphamide (Cytoxan), chlorambucil (Amboclorin), and melphalan (Alkeran)

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of azathioprine, there are no specific foods that you must exclude from your diet when receiving this medication.

Before taking azathioprine, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to azathioprine or to any of its ingredients
• have liver problems
• have kidney problems
• have an inflammatory bowel disease such as Crohn’s or ulcerative colitis
• have blood problems
• have any type of infection
• are scheduled to receive a vaccine
• are scheduled to receive surgery
• have a genetic deficiency with a specific enzyme called the TPMT enzyme
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Azathioprine falls into category D. It has been shown that use of azathioprine in pregnant women caused some babies to be born with problems. However, in some serious situations, the benefit of using this medication may be greater than the risk of harm to the baby.

Whenever possible, use of azathioprine in pregnant patients should be avoided. This drug should not be used for treating rheumatoid arthritis in pregnant women.

Avoiding pregnancy while taking azathioprine is recommended in women of childbearing potential.

Tell your doctor if you are breastfeeding or plan to breastfeed.

Tell your doctor if you are breastfeeding or plan to breastfeed.

The use of azathioprine in nursing mothers is not recommended. azathioprine or its products are transferred at low levels in breast milk. Because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using azathioprine.

Take azathioprine exactly as prescribed.

Oral:

• This medication comes in tablet form and is taken once or twice a day, with or without food.
• If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of azathioprine at the same time.

Injectable:

• This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends will be individulized for each patient. 

The dose may be based on the following:

• the condition being treated
• how you respond to this medication
• other medications you are taking
• your weight
• your renal function

Rheumatoid arthritis

The initial dose of azathioprine should be approximately 1.0 mg/kg (50 to 100 mg) given as a single dose or on a twice daily schedule. The dose can be titrated up if needed and if there are no serious toxicities to a maximum 2.5 mg/kg/day.

Kidney transplant

The initial dose is usually 3 to 5 mg/kg daily, beginning at the time of transplant. Dose reduction to maintenance levels of 1 to 3 mg/kg daily is usually possible.

If you take too much azathioprine, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If azathioprine is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

• Store azathioprine at room temperature.
• Protect from light.
• Keep this and all medicines out of the reach of children.

Chronic immunosuppression with azathioprine, a purine antimetabolite increases risk of malignancy (cancer) in humans. Reports of malignancy include post-transplant lymphoma and hepatosplenic T-cell lymphoma (HSTCL) in patients with inflammatory bowel disease. Physicians using this drug should be very familiar with this risk as well as with the mutagenic potential to both men and women and with possible hematologic toxicities. Physicians should inform patients of the risk of malignancy with azathioprine.